The present invention relates generally to blood product storage containers, and more particularly, relates to an improved container for the storage of blood products which includes a microporous membrane for detecting and indicating changes in selected characteristics of the blood product contained therein and for preserving selected storage conditions.
In the medical field, it is critical that a supply of various blood products, such as platelets, plasma, and red blood cells, be readily available. Such products are preferably stored for immediate use, generally in flexible bags which can be easily attached to blood tubing sets for use by the patient.
Often, however, blood products are stored for periods of time before use. During these storage periods, environmental factors may cause the quality of the blood product to be affected, making the use of the blood product questionable or inadvisable. For instance, changes in temperature, changes in the pH level of the blood product, and changes in the electrolyte balance of the blood product will compromise the quality of the blood product. Likewise, if bacteria have entered the storage container and contaminated the blood product, a decrease in glucose levels may be detected, or an increase in carbon dioxide production may be detected, indicating that the blood product is no longer of a useable quality.
Such changes in the quality of the blood product are generally undetectable by visual inspection. Instead, a sample of the blood product may have to be removed from the storage container and tested for assurance that the quality of the product is satisfactory.
Various devices have been created to address the problems associated with monitoring the quality of stored blood products. For example, the apparatus described in U.S. Pat. Nos. 4,952,498 and 5,051,360, both to Waters, are adapted to detect gas-generating activity of microorganisms in a storage vessel. A portion of the vessel inflates to indicate existence of an increase in pressure within the vessel, caused by microorganism activity, which is detectable by visual monitoring.
U.S. Pat. No. 5,514,106 to DSilva discloses a storage bag having means for indicating the status of the contents of the bag, specifically, whether the contents have been subjected to a treatment process, such as illumination or radiation sterilization. Overlapping portions of the bag form a flap having at least one hole punched therethrough which is capable of detection by a sensor to indicate treatment of the fluid within the bag. The bag may included a polarizing piece.
Likewise, the devices shown in WO92/19284 and JP406007410 each disclose blood storage bags having indicia that visibly change when irradiated to indicate that the contents have been exposed to radiation.
U.S. Patent No. to Malcolm et al discloses a testing and dispensing apparatus for measurement of the pH level of the contents contained in a storage vessel, comprising a dispensing tube and standard pH indicator removably received within the tube.
U.S. Pat. Nos. 2,856,885 and 2,856,930 to Huyck et al each disclose temperature indicators for blood storage containers which specifically indicate whether the contents of a blood storage container have reached a temperature exceeding 50xc2x0 F. The devices utilize a tube filled with a selected indicator liquid.
In a seemingly unrelated technical area, known as separation technology, plugged pore membranes have been employed with storage containers, specifically to preserve and maintain the contents stored therein. Generally, a plugged pore membrane is used to separate two substances, and consists of a membrane having a number of small and larger pores plugged with selected polymers. The polymers are erodible upon exposure to certain environmental conditions. Erosion of the polymer allows one of the substances to pass through the membrane, depending on the size of the pores from which the polymer was eroded, thereby treating the second substance and preventing spoilage and promoting preservation.
As U.S. Pat. No. 5,261,870 to Hammerstedt et al discloses, suitable applications include cell cultures and cryobiology, preingestion preservation and storage of food and pharmaceuticals, shelf-life extension of polymers, proteins and other products, and the containing, transporting and dispensing of active agents, including cells, herbicides, pesticides, fertilizers, and cell growth nutrients or other biologically active agents for use in laboratory or industrial settings. The Hammerstedt separation barrier is specifically contemplated for the preservation of rooster and turkey sperm for use in commercial artificial insemination applications.
Erodible polymers and microspheres have been employed in the pharmaceutical industry, specifically, in dissolvable capsules and even silicon rubber compounds, from which a drug is slowly released and administered to a patient over periods of hours or days as the polymer is dissolved by exposure to certain substances or environmental factors.
None of the above described art, however, has addressed the problem of conveniently monitoring and sustaining the quality of stored blood products by incorporating a responsive, microporous membrane into a blood storage container. Accordingly, a need exists for a blood storage bag adapted to detect and indicate changes in selected characteristics of blood products, and for a storage bag which also may initiate the addition of buffers and nutrients to the product when needed to sustain or improve the quality of the product, preventing spoilage and waste.
In order to meet the aforementioned needs, it is an important aspect of the present invention to provide a flexible bag for the storage of blood products, including a membrane either attached to an interior surface of at least one of the walls of the flexible bag to define a contained space between the membrane and the wall, or free-floating within the inner volume of the bag. The contained space may contain a selected chemical agent.
The membrane has a plurality of pores therein to allow passive communication between the contained space or the agent and the blood product. In the preferred embodiment, the pores are filled with an erodible substance, such as a powder, which is responsive to a selected characteristic of the blood product, causing the pores to have a relatively smaller pore size at a first value of the selected characteristic and a relatively larger pore size at a second value of the selected characteristic.
It is also contemplated that the membrane itself may be composed of a material responsive to the selected characteristic of the blood product, such that the unfilled pores themselves are responsive to the selected characteristic, having a relatively smaller pore size at a first value of the selected characteristic and a relatively larger pore size at a second value of the selected characteristic.
It is yet another aspect of the present invention to provide the flexible bag described above in which the selected characteristic is pH level, where a fully closed pore state preferably occurs when the pH of said blood product is 6.4 or greater, and where the fully opened pore state occurs when the pH of said blood product is 6.2 or less.
It is a still further aspect of the present invention to provide a flexible bag as described above wherein the blood product is treated with buffers or nutrients when the pores begin to open, or the erodible substance begins to dissolve, in response to changes in the selected characteristic to preserve and maintain the quality of the blood product.
It is another aspect of the present invention to provide a method for monitoring the quality of a blood product stored in a flexible bag, including the steps of providing a membrane having a plurality of pores within the inner volume of said bag, and adding a selected chemical agent to said contained space, the agent in passive communication with said blood product through said pores.
It is a further aspect of the present invention to provide an improved apheresis system and an apheresis system tubing set including the above described flexible bag and microporous membrane attached to an interior surface of at least one wall of the flexible bag or free-floating within the contents of the bag.